The aim of this application is to develop, prototype, validate, manufacture and commercialize a new, generalized microbiosensor designed for non-human use and based on functionalized nanoparticles. The microbiosensors produced will enable in vivo monitoring of a wide range of non-electroactive, neurologically relevant analytes, including, but not limited to, glucose, glutamate, lactate, choline, histamine, D-serine, and ethanol. The design can be extended to multiple conjoined capillaries to provide an array of biosensors for the simultaneous monitoring of multiple analytes, with high temporal and spatial resolution, which causes minimal damage to the surrounding tissue. The specific aim for Phase I is to demonstrate feasibility by prototyping and characterizing a tissue implantable enzyme functionalized nanoparticle microbiosensor that is suitable for in vivo brain measurements and extensible to multianalyte microbiosensor arrays. The proposed microbiosensor will allow researchers to target smaller subregions of the brain that would be damaged by currently available probes. This, in turn, will lead to a better understanding of function and assist in quantifying drug response. The proposed microbiosensor design can also be adapted to the simultaneous monitoring of multiple analytes within a single region of space. Turn-key tools that allow an enhanced level of specificity and granularity will be widely useful in research on the causes, prevention, diagnosis, and treatment of neurological disorders, and this will lead to new discoveries. Pinnacle will lead this application and work in conjunction with an interdisciplinary consortium of three leading scientists at the University of Kansas. Professor Judy Wu possesses extensive experience in materials science and nanofabrication techniques, Professor Mark Richter is skilled in protein engineering, and Professor George Wilson brings over 30 years of experience in biosensor development to the project. The facilities and equipment available at Pinnacle, and the various University of Kansas laboratories, will provide the resources required to successfully complete this project. Innovative aspects of this application include the use of active enzyme functionalized nanoparticles as the sensing element, and the controlled electrophoretic deposition of these nanoparticles. Also novel is a design that maximizes oxygen reuse and hydrogen peroxide detection efficiency. This will lead to linear microbiosensors with high sensitivity for the analyte being monitored. Extensive preliminary results are presented in the application. These results are the foundation for this Phase I effort. Overall, worldwide biosensor sales in FY2009 were $6.9 billion with 31 percent of the sales due to human glucose sensors. Pinnacle is an established manufacturer of biosensors and is well positioned to introduce this new class of biosensors to a broad pre-clinical market. PUBLIC HEALTH RELEVANCE: In the United States, over 1000 disorders of the brain and nervous system result in more hospitalizations than for any other disease group including heart disease and cancer. The quality of life, and economic, cost of brain and nervous system related disorders, is staggering. These disorders disrupt the lives of more than 50 million Americans each year and costs exceed $400 billion.